The efficacy of ascofuranone in a consecutive treatment on Trypanosoma brucei brucei in mice
The efficacy of ascofuranone in a consecutive treatment on Trypanosoma brucei brucei in mice
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DOI：
10.1016/s1383-5769(03)00012-6
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发表时间：
2003-06-01
影响因子：
1.9
通讯作者：
Ohta, N
中科院分区：
文献类型：
--
作者：
Yabu, Y;Yoshida, A;Ohta, N
发现连续给予不含甘油的阿司呋喃酮对小鼠布氏锥虫感染具有治疗效果。将子囊呋喃酮的悬浮液（25-100 mg/kg）每24 h腹膜内给予锥虫感染的小鼠，连续1-4天，并将效力与口服治疗进行比较。腹腔给药，所有小鼠用100 mg/kg子囊呋喃酮连续4天治疗治愈。相反，口服治疗需要更高剂量的子囊呋喃酮（400 mg/kg）连续8天才能治愈小鼠。腹膜内给药后，寄生虫血症得到强烈抑制，几乎所有细长血流形式的寄生虫在第3天变为短截形式，并且在给药开始后4天寄生虫已被消除。这些子囊呋喃酮诱导的短短截形在形态上类似于T. B.布鲁氏菌GUTat 3.1.然而，泛醇氧化酶活性的性质，这是目标的ascofuranone，在线粒体分离前和处理后，几乎相同。泛醇氧化酶的酶活性在处理后的一天内仅下降到约30%，然后保持在几乎相同的水平。在本研究中，我们改进了不含甘油的子囊呋喃酮给药方案，并证明连续给药子囊呋喃酮在T. B.布氏杆菌感染的小鼠。我们目前的研究结果强烈表明，连续给药的ascofuranone可能是一种有效的化疗非洲锥虫。(C)2003爱思唯尔科学爱尔兰有限公司保留所有权利。
Consecutive administration of ascofuranone without glycerol was found to have therapeutic efficacy against Trypanosoma brucei brucei infection in mice. A suspension of ascofuranone (25-100 mg/kg) was administrated intraperitoneally every 24 h for 1-4 consecutive days to trypanosome-infected mice and efficacy was compared with oral treatment. With intraperitoneal administration, all mice treated with 100 mg/kg ascofuranone for 4 consecutive days were cured. On contrary, with oral treatment a higher dose of ascofuranone (400 mg/kg) was needed for 8 consecutive days to cure the mice. With intraperitoneal treatment, parasitemia was strongly suppressed, with almost all long slender bloodstream forms of the parasite changed to short stumpy forms by day 3 and the parasites have been eliminated 4 days after the start of treatment. These ascofuranone-induced short stumpy forms were morphologically analogous to the stumpy forms 2 days after peak parasitemia of pleomorphic clone of T. b. brucei GUTat 3.1. However, the properties of ubiquinol oxidase activity, which is the target of ascofuranone, in mitochondria isolated from before and after treatment, were almost same. The enzymatic activities of ubiquinol oxidase were only decreased to approximately 30% within a day after treatment, and then kept at nearly the same level. In the present study, we have improved regimen for administration of ascofuranone without glycerol, and demonstrated that consecutively administrated ascofuranone showed trypanocidal effects in T. b. brucei infected mice. Our present results strongly suggest that consecutive administration of ascofuranone may be an effective chemotherapy for African trypanosomiasis. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.